Evidence has been accumulated in this project for the compartmentalization of intracellular GH and PRL storage in both normal pituitary and GH sub 3 rat pituitary tumor cells. For GH, at least, these compartments are differentially dischargeable, are differentially filled, and can be shown to depend upon subcellular microtubular/microfilamentous structures. Apparently, both somatostatin and thyroid hormone activity may be necessary for the maintenance of the immediate release pool (quantitatively the smaller) from the late release pool (quantitatively the larger). In fact, all hormone storage appears to depend upon the tonic presence of hypothalamic influence since storage but not synthetic ability is lost when normal cells are isolated from tonic influences in vivo and in vitro, and preliminary results suggest that then storage function can be at least partially restored by prolonged exposure to somatostatin. Recent work has suggested that direct feedback of the secreted hormone upon its cell of origin may regulate intracellular degradation of stored hormone. The current effort of this grant is directed at elucidating this possibility and using it as a focal point for coordinating evidence already accumulated about intracellular control mechanisms.